Over the past years the Division of Oncology has been involved in a continuing program of experimental and clinical marrow transplantation directed toward the treatment of patients with otherwise fatal hematologic diseases. The clinical studies have involved conditioning of the patient with high doses of cyclophosphamide, or total body irradiation, or a combination of both followed by infusion of marrow from either a syngeneic sibling (monozygous twin) donor, or a sibling matched with the recipient at the major human histocompatibility complex. A number of patients have become long-term survivors with neither recurrence of their original disease nor with occurrence of graft-vs-host disease (GVHD). Many patients, however, have died either from recurrent disease, or more frequently, from complications related to the transplant. Further improvement of clinical marrow grafting results hinges upon progress and better understanding in at least four areas of study: (1) Recovery of immunologic reactivity in marrow graft recipients. (2) Elucidation of mechanisms of stable graft-host tolerance and of GVHD. (3) Methods of recognizing and overcoming sensitization to transplantation antigens due to blood transfusions. (4) Detection of cell-mediated immunity to leukemia-associated antigens and use of marrow grafting as immunotherapy. With increased experience in the field of clinical marrow grafting we have begun turning our attention to these questions. It is the objective of this project to conduct immunologic investigations in these four areas of study.